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Residual HBV DNA and pgRNA viraemia is associated with hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy
Lung-Yi Mak, Qi Huang, Danny Ka-Ho Wong, Luisa Stamm, Ka-Shing Cheung, Kwan-Lung Ko, Ran Yan, Lea Ouyang, James Fung, Wai-Kay Seto & Man-Fung Yuen
Journal of Gastroenterology volume 56, pages479–488(2021)Cite this article
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Abstract
Background
We aimed to assess whether residual hepatitis B virus (HBV) viraemia is associated with HCC development.
Methods
This is a case–control study of 104 patients [52 HCC and 52 non-HCC (matched with age, gender, cirrhosis and treatment duration)] on ≥ 3 years entecavir (ETV) with unquantifiable HBV DNA by Cobas Taqman assay v2.0 (Roche Diagnostics; lower limit of quantification [LLOQ] 20 IU/mL). Serial sera within 1, 1–2, and > 2 years prior to HCC diagnosis or last follow-up (LFU) were measured for HBV DNA and pre-genomic (pg) RNA using a highly sensitive semi-quantitative PCR assay with lower limit of detection of 10 IU/mL and LLOQ of 51.5 IU/mL, respectively.
Results
Among the 104 patients (80.8% male, median age 61.2 years old, 38.5% cirrhosis, median duration of ETV 45.5 months), 38.5% and 9.6% HCC patients had undetectable serum DNA and pgRNA, respectively, compared to 65.4% and 36.5% in non-HCC patients; P = 0.005 & 0.001, respectively, at the time of HCC diagnosis/LFU. Detectable HBV DNA and pgRNA were associated with a higher 2-year risk of HCC development (HR 2.79, 95% CI 1.424–5.468 & HR 4.544, 95% CI 1.07–19.289, respectively). No significant differences were observed for qHBsAg levels between HCC and non-HCC patients.
Conclusions
More than 50% CHB patients on ETV with HBV DNA < LLOQ by standard assay had persistent viraemia as determined by a more sensitive assay. Detectable HBV DNA or pgRNA by more sensitive assays was associated with HCC development. More potent viral suppression is required to further reduce the risk of HCC. |
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